DNA Health > Inflammation
IL-1A 4845 G>T or -889 C>T
IL-1B 3954 C>T & -511 A>G, & IL-1RN 2018 C>T
Among the first genes activated by any initiating factor (any challenge to a tissue) are the genes IL-1 and TNF-alpha. Both these molecules are capable of activating each other and are critical components of the inflammatory process.
IL1 Gene Detail
IL-1 has been increasingly implicated as an important leverage point in the inflammatory cascade and so IL-1 expression is key in the pathogenesis of several chronic diseases.
The biological activity of IL-1 involves several components such as:
- IL-1 alpha, which is cell-bound (encoded by IL-1A)
- IL-1 beta, a secreted cytokine, (encoded by IL-1B)
- IL-1 receptors
- IL-1 receptor antagonist (encoded by IL-1 RN), which is a negative regulator of the pro-inflammatory response.
Active IL-1B is produced by cleavage of pro-IL 1B by inflammasome-mediated caspase-1 or neutrophil proteases.
IL-1A is produced and accumulated in the cell and is released upon cell necrosis thereby serving as an alarmin. Once activated, IL-1A and IL-1B act as potent proinflammatory cytokines at the local level, triggering vasodilation and attracting monocytes and neutrophils to sites of tissue damage and stress. IL-1 cytokines are crucial for the induction of matrix enzymes and serve as potent mediators of tissue damage by altering cartilage and bone homeostasis. Systemically IL-1 cytokines foster the hypothalamic fever response and promote hyperalgesia. Uncontrolled IL-1 activation is a central component of some inflammatory diseases.
Certain genetic variations in IL-1A and IL-B and IL-1 RN lead to a more active inflammatory response, and have been associated with increased risk for a number of chronic diseases.
IL-1A 4845 G>T, IL-1A -899 C>T, IL-1B 3954 C>T, IL-1B -511 A>G, IL-1RN 2018 C>T
Risk allele = IL-1 positive
IL-1A 4845 G>T or -889 C>T = T alleles lead to an increase expression of IL-1A.
IL-1B 3954 C>T & -511 A>G = T allele and C allele respectively lead to an increase expression of IL-1B.
IL-1RN 2018 C>T = T allele lead to a decreased receptor antagonist function and increased risk for periodontitis and certain cancers.
The combination of IL-1 SNPs of an individual have been linked to differing clinical trajectories of certain diseases, of course also depending on the assaulting stimulus present.
IL-1 SNPs, in various combinations, are used in a complex algorithm to determine IL1 status; either being IL-1 positive, or IL-1 negative.
In general, individuals with genotypes that match an IL-1 positive result have been associated with increased IL-1 protein plasma concentrations, increased concentrations of CRP, as well as increased levels of IL-1 alpha and beta in gingival fluid.
IL-1 positive genotypes have been linked with several pro-inflammatory chronic diseases, including periodontitis, coronary artery disease, certain autoimmune diseases and cancers.
Strategies that have been shown to act directly on IL-1 gene expression and inhibit secretion of pro-inflammatory markers, include the following:
- Phytonutrient rich foods such as blueberries and blackberries that contain compounds such as resveratrol, anthocyanins and dehydro-ascorbate.
- Increasing omega 3 fatty acids. Avoiding a high intake of omega 6 fatty acids and eating a diet rich in omega 3 fatty acids, from appropriately-sourced oily fish, is recommended.
Evidence-based recommendations targeting more general anti-inflammatory strategies include:
- Weight management
- Engaging in moderate exercise
- Cessation of smoking
Also, following a Mediterranean style diet, has been associated with an improved inflammatory profile.
Interleukin 1 genetics, inflammatory mechanisms, and nutrigenetic opportunities to modulate diseases of aging